This invention relates to spectroscopic methods using nuclear magnetic resonance (NMR). More specifically, the invention relates to methods for performing spatially localized NMR chemical shift imaging.
Atomic nuclei having net magnetic moments placed in a static magnetic field, B.sub.o, oscillate or precess about the axis of field B.sub.o at an NMR (Larmor) frequency .omega. given by the equation EQU .omega.=.gamma.B.sub.o ( 1)
in which .gamma. is the gyro-magnetic ratio, constant for each NMR isotope. The frequency at which the nuclei precess is primarily dependent on the strength of the magnetic field B.sub.o, and increases with increasing field strength. Chemical shifts occur where the NMR frequency of resonant nuclei of the same type in a given molecule differ because of different magnetic environments produced by differences in their chemical environment. For example, electrons partially screen the nucleus from the externally applied magnetic field and thereby affect its resonant frequency. The degree of shielding caused by the electrons depends on the environment of the nucleus, and thus the chemical shift spectrum of a given molecule is unique and can be used for identification. Because the resonant frequency, hence the absolute chemical shift, is dependent on the strength of the applied field, the chemical shift is expressed as fractional shift in parts-per-million (ppm) of the resonance frequency relative to an arbitrary reference compound. By way of illustration, the range of chemical shifts is about 10 ppm for protons (.sup.1 H), 30 ppm for phosphorus (.sup.31 P), and 200 ppm for carbon (.sup.13 C). In order to discern such small chemical shifts, the homogenity of field B.sub.o must exceed the differences in chemical shifts of the peaks in the spectrum and typically is much better than 1 part in 10.sup.6 (1 ppm).
In conventional NMR spectroscopy, chemically shifted signals are observed from the whole of the NMR sample placed in the region to which the NMR coil is sensitive. While this is satisfactory for studying the chemical structure of a homogeneous sample, to enable discrimination of normal and abnormal conditions in biological or medical diagnostic applications where samples are in general heterogeneous, it is desirable to obtain spatial information concerning the chemically shifted signal components. For instance, phosphorus exists in the body attached to key molecules involved in metabolism. The localized measurement of the amplitudes of the phosphorus spectral lines could provide a direct and unique measure of cellular energy and of the state of health of the tissue in the region examined.
In the past, surface coil, topical, and sensitive point NMR methods have been used to perform localized chemical shift spectroscopy. These methods are described, respectively, by J. J. H. Ackerman et al., Nature, Volume 283, page 167 (1080); R. E. Gordon et al., Nature, Volume 287, page 736 (1980); and P. A. Bottomley, Journal of Physics E: Scientific Instruments, Volume 14, page 1081 (1981). In all of these methods the data is gathered from a single localized region at a time so that many localized regions must be individually observed in order to obtain sufficient spatial data to construct an entire image.
More efficient data collection methods have been proposed in which the NMR imaging data is gathered simultaneously from many points. One example is the selective excitation zeugmatography method described by P. C. Lauterbur in The Journal of the American Chemical Society, Volume 97, page 6866 (1975). Another example is the .sup.31 P spectroscopic zeugmatography method described by P. Bendel et al., in The Journal of Magnetic Resonance, Volume 38, page 343 (1980).
The method disclosed by Lauterbur, et al. is based on the projection reconstruction method of NMR spin density imaging. In this method, each one-dimensional projection is obtained point-by-point by selective excitation of a plane of spins lying perpendicular to a magnetic field gradient oriented at the projection angle. The Fourier transform of the NMR signal in the absence of the gradient yields the chemical shift spectrum of the selected plane of spins and corresponds to one point in the projection. Subsequent points in the projection are obtained by changing the main magnetic field strength. Upon completion of a projection, the gradient is reoriented within the desired imaging plane and the process repeated to obtain spectra for each point in all of the projections. Except for the inherent RF field inhomogeneity afforded by the receiver coil geometry, no provision for localization in the third dimension is made. The selective excitation pulses employed are amplitude-modulated (tailored) pulses of long duration to give narrow excitation bandwidths.
The method disclosed by Bendel, et al. is also based on reconstruction from projections. In order to obtain spatial resolution of the chemical shift spectra, magnetic field gradients, at a predetermined projection angle, are applied while the NMR signal is recorded so as to broaden the individual spectral lines of the spectrum. Multiple projections are obtained by changing the orientation of the projection angle. A disadvantage of this method is the limited resolution obtained of the individual projections of each compound due to the relatively weak magnetic gradient field which must be used: If stronger gradient fields are used, the spectral lines are so broadened that they overlap to such an extent that the chemical shift information is effectively lost. In general, this is also the reason why conventional NMR spin density imaging methods fail to yield chemical shift data. In such methods, the NMR signal is typically observed in the presence of strong gradient fields which provide spatial distribution information of the nuclear spin density, but which obliterate the chemical shift spectrum. The effects of gradients and chemical shifts on the NMR signal are similar and cannot be distinguished without prior knowledge of either spatial structure or chemical shift.
It will be readily appreciated, therefore, that, although the inventive methods described and claimed herein bear similarity to various NMR proton imaging techniques, there are important differences necessitated by the fact that the NMR signal (hence spatial localization data obtained) must be observed in the absence of magnetic field gradients. Moreover, chemical shift imaging is a five-dimensional problem (three spatial variables, intensity, and chemical shift) that is significantly more difficult than NMR imaging which involves only four variables (three spatial variables, plus intensity).
Accordingly, it is an object of the invention to provide methods for localized NMR chemical shift imaging.
It is another object of the invention to provide NMR chemical shift imaging methods in which the NMR signal is observed in the absence of magnetic field gradients.
It is still another object of the invention to provide efficient NMR chemical shift imaging methods wherein data is collected from many sample regions simultaneously to reduce data acquisition time.